The aetiology of chronic prostatitis is not understood. The aim of this study is to investigate an autoimmune hypothesis by looking for T cell proliferation in response to proteins of the seminal plasma. We studied peripheral blood mononuclear cell proliferation from 20 patients with chronic prostatitis and 20 aged-matched controls in response to serial dilutions of seminal plasma (SP) from themselves (autologous SP) and from a healthy individual without the disease (allo-SP). We found that the patients have a statistically greater lymphocyte proliferation to autologous SP at the 1/50 dilution on day 6 compared to controls (P = 0 x 01). They also have a greater proliferation to allo-SP on both day 5 (P = 0 x 001) and day 6 (P = 0 x 01) at the same dilution. Using a stimulation index (SI) of 9 to either autologous SP or allo-SP on day 6 at the 1/50 dilution as a definition of a proliferative response to SP, then 13/20 patients as compared to 3/20 controls showed a proliferative response to SP (P = 0 x 003, Fishers exact test). These data support an autoimmune hypothesis for chronic prostatitis.