Basal cell hyperplasia in the prostate is often viewed as a transition zone proliferation, related to usual, nodular glandular, and stromal hyperplasia. Basal cell hyperplasia in the prostatic peripheral zone, the most common site for development of prostatic intraepithelial neoplasia and carcinoma, has not been previously characterized. We characterized the incidence and histomorphological attributes of basal cell hyperplasia in a series of 500 consecutive sextant needle core biopsy samples and in 26 completely embedded prostate glands from radical prostatectomy specimens. Comparative proliferation indices (by MIB-1 staining) and apoptotic indices (by TUNEL labeling) were quantitated for peripheral zone versus transition zone basal cell hyperplasia versus normal basal cells. The incidence of basal cell hyperplasia in prostate needle biopsy tissue was 10.2% (51 of 500 cases). Usual basal cell hyperplasia was detected in 8.2% of the 500 cases, and basal cell hyperplasia with prominent nucleoli, in 2.0% of cases. Basal cell hyperplasia in needle biopsy tissue was typically focal and associated with inflammation, which was usually lymphocytic, in 84% of cases. Peripheral zone basal cell hyperplasia was found in 23% of whole prostate glands. Peripheral zone basal cell hyperplasia was not observed to be in direct physical continuity with intraepithelial or invasive neoplasia. Peripheral zone and transition zone basal cell hyperplasia exhibited similar mean proliferation and apoptotic indices, at 1% and 0.07%, respectively. This proliferation index was elevated, and apoptotic index was decreased, relative to normal basal cells (P = 1 x 10(-7)). Basal cell hyperplasia in the peripheral zone is present in a significant minority of prostate needle biopsy samples and whole prostate glands. The presence of prominent nucleoli in basal cell hyperplasia may cause diagnostic concern for a neoplastic proliferation. The increase in cell number in basal cell hyperplasia appears to be due to a coordinate increase in proliferation index coupled with a diminished apoptotic index. The presence of inflammation in the majority of basal cell hyperplasia foci suggests that peripheral zone basal cell hyperplasia in untreated patients may represent a stereotyped response to injury such as that sustained because of inflammation.