['In conventional treatment planning for permanent I-125 prostate implants, it has been suggested that lower seed activities result in more homogeneous dose distributions and also less overdose of the critical structures. We sought to determine if this hypothesis holds by analyzing treatment plans constructed using an automated optimized approach.', 'We studied treatment plans for 10 patients using mixed-integer programming and the branch-and-bound method. Two mixed-integer models (that yielded somewhat different treatment plans) were developed: a "basic" model and a "dose homogeneity" model. For each resulting treatment plan, we examined dose homogeneity (by evaluating the dose non-uniformity ratio [DNR] and the full-width half-maximum [FWHM] of the differential dose-volume histogram [DVH]) as a function of three different source activities (0.35 mCi, 0.44 mCi, and 0.66 mCi). In addition, target coverage and critical structure dose distributions were evaluated. Plans using multiple source activities were also evaluated for resulting dose inhomogeneities.', 'The homogeneity model results in a more homogeneous dose distribution than the basic model. DNR is lowered by an average of 42% (standard deviation [SD] = 19%), 39% (SD = 21%), and 33% (SD = 21%) for the 0.35 mCi, 0.44 mCi, and 0.66 mCi seeds, respectively, when the homogeneity model is employed over the basic model. Corresponding average decreases in the FWHM of the DVH for 0.35 mCi, 0.44 mCi, and 0.66 mCi, respectively, are 29 Gy (SD = 28 Gy), 24 Gy (SD = 22 Gy), and 27 Gy (SD = 13 Gy). Seeds of 0.35 mCi and 0.44 mCi result in the lowest DNR and narrower FWHM of the DVH relative to 0.66 mCi seeds. In general, the 0.44 mCi seeds produce greater target coverage and require fewer seeds and needles than the 0.35 mCi seeds. Although 0.66 mCi seeds result in the greatest target coverage, they yield highest critical structure doses. They also yield solutions requiring the least number of seeds and needles. However, the dose distributions from 0.66 mCi seeds are highly inhomogeneous. Multiple source activities in the same treatment plan produce dose distributions that are comparable in homogeneity to 0.44 mCi seed implants.'] Do dose homogeneity as a function of source activity in optimized I-125 prostate implant treatment plans?