['Retinoic acid (RA) has a critical role during development of the retina. We investigated RA effects on photoreceptor apoptosis and differentiation, and the intracellular pathways involved.', 'Rat retinal neuronal cultures were supplemented with RA with or without docosahexaenoic acid (DHA), a photoreceptor survival factor, and photoreceptor apoptosis and differentiation were evaluated at different times of development. To investigate the intracellular pathways activated by RA, the levels of phosphorylated (P) ERK and P-p38 in cultures with or without RA, and the effect of pretreatment with SB203580, a p38 specific inhibitor, on apoptosis and differentiation were evaluated.', 'RA addition at day 0, when cells still were proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. RA stimulated opsin and peripherin expression, and neurite outgrowth regardless of the time of development. Addition of RA at day 0, but not at day 2, rapidly increased P-p38 levels, but did not affect P-ERK levels. p38 inhibition completely prevented RA-induced apoptosis, and partially decreased differentiation. DHA prevented apoptosis and additively increased differentiation, without affecting RA activation of p38.'] Does retinoic acid promote apoptosis and differentiation in photoreceptors by activating the P38 MAP kinase pathway?