The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03 +/- 1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42 +/- 1.06 ng ml(-1); P = 0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60 +/- 1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89 +/- 1.43 ng ml(-1); P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86 +/- 3.64 ng ml(-1)) compared to preoperative level (5.11 +/- 2.47 ng ml(-1)., P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P = 0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.