Identification of loss of heterozygosity on specific genetic loci is crucial for understanding the pathogenesis of prostate cancer at the molecular level. This is especially important because the deleted regions may contain putative tumor suppressor genes. Chromosome 3p loss appears to be frequently associated with various epithelial cancers. To our knowledge, there is no report on loss of heterozygosity (LOH) of chromosome 3 in human prostate cancer. The present study was designed to investigate the LOH on chromosome 3p in microdissected samples of delineated regions of normal and invasive carcinoma areas of prostatic epithelium from the same tumor sections. For this purpose, DNA was extracted from microdissected normal and tumor cells of 38 prostate cancers, amplified by PCR and analyzed for LOH on chromosome 3p using 6 different polymorphic DNA markers (D3S1560, THRB, D3S647, D3S1298, D3S1228 and D3S1296). Our results suggest that LOH was identified in 34 of 38 cases (89%) with at least one marker. Twelve of 30 informative cases showed LOH at D3S1560; 18 of 22 informative cases showed loss at THRB; 20 of 38 informative cases showed deletion at D3S647; 16 of 38 informative cases showed loss at D3S1298; 12 of 34 informative cases showed LOH at D3S1228; and 6 of 34 informative cases showed LOH at D3S1296 regions. Our results suggest that the LOH is on the 3p24-26 and 3p22-12 regions of the short arm of chromosome 3, indicating 2 discrete areas of deletion on chromosome 3p. The deletion at 3p24-26 and 3p22-12 was not related to the stage or grade of the tumor.