AbstractChronic bacterial prostatitis, that has become resistant to antibiotic therapy, remains a frustrating clinical entity for both clinicians and patients. Twenty men with a history of documented bacterial prostatitis, that had become resistant to appropriate antibiotic therapy, were studied in an attempt to determine where the bacteria had become localized, and possibly explain their survival in a relative bactericidal environment. The antibiotics were discontinued for 4 weeks, and cultures of the expressed prostatic secretions, tissue biopsies, histology, and ultrastructure were correlated. Twelve (60%) of the tissue biopsies cultured presumed pathogens. In six of the tissue‐positive cases, the expressed prostatic secretion was negative. Specific electron micrographs demonstrate exopolysaccharide coated micro‐colonies of bacteria firmly attached to the ductal and acinar walls. This mode of growth helps explain some of our difficulties in the diagnosis and treatment of chronic bacterial prostatitis. © 1993 Wiley‐Liss, Inc.