Intravesical inoculation of Proteus mirabilis produced severe prostatitis preceding renal infection in male rats. Inflammation and abscesses predominated in the ventral prostate, while the dorsolateral prostate was relatively spared. Nearly all rats (126 of 130) with prostatitis had associated pyelonephritis, while renal infection was rare (4 of 52) in the absence of prostatitis. Bilateral orchiectomy five weeks before challenge resulted in prostatic ablation and protected against retrograde pyelonephritis. Orchiectomy only three days before challenge gave no protection. Previous reports have suggested a protective role for the prostate due to antibacterial activity in its secretions. It is probable that prostatitis occurs when this activity is overcome. The prostate may then serve as a focus of infection and provide an obstruction; these factors would lead to infection of the urinary tract. Orchiectomy may protect against pyelonephritis, in part, by removing the prostatic focus.