To identify prostate specific antigen (PSA) functions of prognostic significance in regard to treatment with androgen deprivation for prostate cancer we analyzed the pretreatment PSA, PSA half-life, PSA nadirs, times to PSA elevation and PSA doubling times in 245 patients with localized and 78 with metastatic disease who were treated with this modality. There was a direct correlation between the pretreatment PSA and the time to PSA elevation in patients with localized cancer (p = 0.000003) but no significant correlation in those with metastatic cancer. The PSA half-life was highly variable and did not correlate with other PSA functions of prognostic significance. Incremental increases in the PSA nadir correlated with the time to PSA elevation in patients with localized and metastatic cancer (p < 0.000001 and p = 0.00009, respectively), and with other parameters of prognostic significance. The median PSA doubling time in 26 patients with localized cancer in whom distant metastases did not develop (7.5 months) was significantly longer than that in 7 in whom new metastases developed (2.5 months) and in 43 with preexisting metastatic cancer (2.5 months) (p < 0.05 and p < 0.0001, respectively). In the 7 patients with localized cancer in whom metastases developed the median of the ratios of the PSA when the metastases were manifest and the pretreatment PSA was 0.14, and in 24 patients with preexisting metastatic cancer the median of the ratios of the antemortem PSA and the pretreatment PSA was 1.2. These data show that PSA synthesis by prostate cancer is reduced after androgen deprivation but that the PSA nadir and PSA doubling time following treatment provide important prognostic information.