The post-diagnostic changes in the free to total PSA ratio in the serum of patients with prostate carcinoma, after the initiation of endocrine treatment were examined. Two-week pretreatment with either chlormadinone acetate (100 mg/day) or flutamide (375 ng/day) was administered orally to 14 patients with newly diagnosed advanced prostate carcinoma (clinical stage was C in 2, Dl in 1 and D2 in 11). Then the LH-RH analogue was injected. Total and free PSA in the serum of these patients were measured every 4 weeks by the Ab bead PSA (Eiken) and the recently developed assay for free PSA by Eiken, respectively. The follow-up period ranged from 3 to 9 months with a median of 6 months. Levels of both total and free PSAs decreased significantly following the endocrine treatment, while free to total PSA ratio at 4 to 16 weeks after the start of LH-RH analogue was increased significantly compared to the pretreatment level (p < 0.05). These findings suggest that the rate of decrease of complex PSA during the first 4 months after the beginning of treatment may exceed that of free PSA in the serum of patients with advanced prostate carcinoma initially treated with endocrine therapy.