Expression of a truncated or extracellular form (p105(erbB-2)) of p185(erbB-2) has been demonstrated in the sera of breast cancer patients. We examined the levels of p105(erbB-2) in the sera of patients with various stages of prostatic adenocarcinoma, in patients with benign prostatic hyperplasia (BPH) and in a series of control male patients hospitalized for illnesses unrelated to the prostate. p105(erbB-2) levels did not differ between the controls and BPH patients or between these groups and patients with stage A, B or C adenocarcinomas. In contrast, serum p105(erbB-2) levels of patients with stage D adenocarcinomas were significantly elevated when compared with either control or BPH patients. There was no correlation between PSA and p105(erbB-2) levels among controls, patients with BPH or patients with prostate cancer. Patients with poorly differentiated tumors (combined Gleason score > 7) or moderately differentiated tumors (combined Gleason score 5-7) had higher p105(erbB-2) levels as compared to patients with well-differentiated tumors (combined Gleason score < 5), though this difference was not statistically significant. There was no correlation between serum p105(erbB-2) levels and p185(erbB-2) expression in malignant tissue, as determined by immunohistochemistry. However, patients with moderate to strong expression of p185(erbB-2) within the adenocarcinomas were approximately 4 times more likely to demonstrate elevated serum p105(erbB-2) levels as compared with patients with low expression of p185(erbB-2).