A previous study of 18 primary or metastatic prostate cancers showed loss of genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim USR et al. (1991) Genes Chromosom Cancer 3:215-220]. The small size and infiltrative nature of primary prostatic tumors have hindered efforts to assess allelic losses by traditional restriction fragment length polymorphism (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of this analysis in early prostate cancer, we have amplified polymorphic microsatellite repeats by polymerase chain reaction (PCR), and have quantitated allelic imbalances with phosphor imaging technology. In this study, 63 primary prostate tumors and matched benign tissues obtained by radical prostatectomy were examined at 28 genetic loci on chromosome 8, all but five of which were located on the short arm. Twenty-nine (46%) of the 63 cases showed loss of at least one locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22, were lost in 28 cases. In 10 of these, losses were observed at all informative loci on the p arm. In another 15 tumors, losses were restricted to subregions of the p arm by loci retained either distally toward the p terminus or proximally at the 8p12-8p21 border, or both. In three tumors, two discrete regions of loss were observed within 8p, separated by several retained loci. Allelic loss of 8p loci was associated with higher tumor grade. These data are complementary to previous reports of allelic deletions in colorectal, hepatocellular, and non-small cell lung cancers and suggest the existence of one or more pleotropic tumor suppressor genes on 8p.