Putative premalignant changes in the prostate have been recognized for a number of years. A variety of synonyms have been given to the most commonly described lesion, characterized by proliferation and dysplasia of the normal two cell layers lining prostatic acini and ductules; prostatic intraepithelial neoplasia (PIN) is the term most often used. A premalignant prostatic lesion should have morphologic features similar to invasive carcinoma (CA), a spatial association with microinvasive cancer arising from the lesion, and should occur at a greater frequency, severity and extent in organs harboring CA. Most definitively, progression from the premalignant lesion into CA should be observed over time. PIN fulfills all but the last of these requirements. High grade PIN is cytologically indistinguishable from prostate carcinoma (CAP). The major differentiating feature between PIN and CAP is the presence, although frequently disrupted, of the basal cell layer in the former. We have studied the basal cell layer in PIN using antibodies to high molecular weight cytokeratins and have found a correlation between PIN grade and the percent disruption of the basal cell layer. The cells making up PIN are phenotypically similar to those of CAP. We have used a variety of markers including cytokeratins, vimentin and the lectin Ulex euroapaeus to demonstrate this similarity. Additionally, we and others have noted decreased PIN immunoreactivity with antibodies directed against prostate specific antigen (PSA) and prostatic acid phosphatase. Other investigators have noted additional phenotypic similarities between PIN and CAP, including the ABH and Lewis antigens. PIN incidence and grade correlate well with the presence of CAP elsewhere in the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)