Human chorionic gonadotropin (hCG) and its P sub-unit (hCGp) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCGp sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCGp can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 3 I YO of patients with hCGP-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCGPspecific proliferative response, whereas no patients with non-hCGfbproductive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCGP were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DO2 haplotype, the T-cell response to hCGp was focused on the hCGP(20-47) peptide. Taken together, these results indicate that hCGp is a tumorassociated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.