A method for labeling intracellular and extracellular targets of leukocytes, comprising the steps of: (a) forming a first combination including: (i) a cellular composition having leukocytes and red blood cells, and (ii) a solution comprising a cross-linking agent suitable for cross-linking intracellular proteins, lipoproteins, and nucleic acids of said leukocytes; (b) forming a second combination including: (i) said first combination, (ii) a solution comprising a detergent suitable to permeabilize said leukocytes and lyse said red blood cells, and further comprising a neutralizing agent having a quaternary ammonium salt or an amine containing compound to neutralize the cross-linking activity of said cross-linking agent, said solution having a pH of 6.5 or lower, wherein the volume of said solution is 1 to 10 times the volume of said first combination, and (iii) a binding agent suitable to bind an intracellular or extracellular target of said leukocytes, wherein said binding agent is added after step (a), and wherein said binding agent is in a binding agent cocktail that includes extracellular and intracellular binding agents; and (c) forming a third combination including: (i) said second combination; and (ii) a solution, wherein the added volume of said solution is equal to or higher than the total volume of said second combination to which the solution is added. (a) forming a first combination including: (i) a cellular composition having leukocytes and red blood cells, and (ii) a solution comprising a cross-linking agent suitable for cross-linking intracellular proteins, lipoproteins, and nucleic acids of said leukocytes; (i) a cellular composition having leukocytes and red blood cells, and (ii) a solution comprising a cross-linking agent suitable for cross-linking intracellular proteins, lipoproteins, and nucleic acids of said leukocytes; (b) forming a second combination including: (i) said first combination, (ii) a solution comprising a detergent suitable to permeabilize said leukocytes and lyse said red blood cells, and further comprising a neutralizing agent having a quaternary ammonium salt or an amine containing compound to neutralize the cross-linking activity of said cross-linking agent, said solution having a pH of 6.5 or lower, wherein the volume of said solution is 1 to 10 times the volume of said first combination, and (iii) a binding agent suitable to bind an intracellular or extracellular target of said leukocytes, wherein said binding agent is added after step (a), and wherein said binding agent is in a binding agent cocktail that includes extracellular and intracellular binding agents; and (i) said first combination, (ii) a solution comprising a detergent suitable to permeabilize said leukocytes and lyse said red blood cells, and further comprising a neutralizing agent having a quaternary ammonium salt or an amine containing compound to neutralize the cross-linking activity of said cross-linking agent, said solution having a pH of 6.5 or lower, wherein the volume of said solution is 1 to 10 times the volume of said first combination, and (iii) a binding agent suitable to bind an intracellular or extracellular target of said leukocytes, wherein said binding agent is added after step (a), and wherein said binding agent is in a binding agent cocktail that includes extracellular and intracellular binding agents; and (c) forming a third combination including: (i) said second combination; and (ii) a solution, wherein the added volume of said solution is equal to or higher than the total volume of said second combination to which the solution is added. (i) said second combination; and (ii) a solution, wherein the added volume of said solution is equal to or higher than the total volume of said second combination to which the solution is added.