The present study was designed to investigate the effects of 13-cis-retinoic acid (13-cis-RA) (100 micrograms/mouse/day) and androgen ablation (castration) alone and in combination on growth of a human prostatic carcinoma line (LNCaP) transplanted to athymic nude mice as an experimental model. The results of these studies suggest that; (1) androgen ablation (castration) significantly decreased the size of LNCaP xenograft as compared to untreated animals; (2) when 13-cis-RA was administered to nude mice carrying established tumors (0.51 +/- 0.04 cm3), the tumor size was significantly reduced as compared to untreated controls (0.65 +/- 0.06 cm3 versus 1.63 +/- 0.12 cm3). About 50% of the animals in this group showed xenografts necrosis followed by complete regression of tumors by five months; (3) the combination of androgen ablation and 13-cis-RA treatment to nude mice carrying tumors showed synergistic effect in decreasing the tumor size. These results indicate that combination therapies based on androgen ablation and retinoid administration may be a useful approach for the treatment of prostate cancer.