Morphologic responses of neoplastic human prostate to long-term explant culture were monitored at serial intervals by LM, TEM and SEM, and compared to normal prostate. Explants were cultured at 37 degrees C in CMRL-1066 supplemented with fetal calf serum and antibiotics. At 0-time culture, normal prostate of young adult males obtained at immediate autopsy, consisted of glandular spaces and ducts lined by columnar to cuboidal secretory epithelial cells and basal cells embedded in fibromuscular stroma. Neoplastic tissue was obtained surgically by transurethral resection (TUR), and consisted of stroma widely infiltrated by well-to moderately-differentiated tumor cells arranged in variable sized, gland-like structures. Secretory activity was evident; basal cells were absent in these glands. During early periods of culture up to several weeks, secretory cells of normal prostate became necrotic. Basal cells remained viable, repopulated acinar structures and epithelialized explant surfaces. At these sites, basal cells, or their derivatives, formed a multicellular epithelium. Exaggerated intercellular spaces separated cells, and synthesis of mucus-like material was seen. Epithelial characteristics included microvilli, junctional complexes, and basal lamina. In marked contrast, tumor cells covered explant surfaces forming an irregular, disorganized layer of squamous-like cells with elongated nuclei and prominent nucleoli. Microvilli, junctional complexes, and basal lamina were poorly developed or absent. Intercellular attachments appeared tenous. Some tumor cells accumulated lipid; synthesis of mucus-like material was not seen. At later intervals of culture up to 10 weeks, synthesis of mucus-like material by basal cells, or their derivatives, declined. Surface cells of neoplastic prostate gradually became more anaplastic in appearance; cells contacted neighboring cells with pseudopodia and filopodia.