The results of the treatment of chronic bacterial prostatitis are disappointing. The current status of antimicrobial and immunological research is described. While both a local and systemic antibody response is demonstrated in acute bacterial prostatis, only a local antibody production is found in chronic bacterial prostatis. This response as reflected in the expressed prostatic secretion is specific for the infecting organism and immunoglobulin A is the major antibody class involved. Drug penetration into the prostate has mainly been studied in dogs and the ideal drug appears to be a lipid-soluble base which will concentrate in the slightly acidic prostatic secretion because of ion-trapping. However, these results are not directly applicable to humans because of the slight alkalinity of human prostatic secretion, the localization of the chronic inflammatory process in the interstitium, and the evidence of an active secretory mechanism for trimethoprim. The clinical consequences of these findings are discussed in relation to several recent studies and the treatment with lipid-soluble bases with a low plasma protein binding over extended periods is recommended.