We studied serum prostate-specific antigen levels in 12 men with benign prostatic hypertrophy treated with a long-acting GnRH analogue, leuprolide, 1 mg (0.2 mL) sc. daily for six months. The average decrease in prostate size measured by ultrasound was 45 percent after six months with concomitant improvement in the obstructive symptoms of prostatism. There was a steady decline in serum PSA levels which paralleled the decrease in prostate size. One patient who discontinued treatment after six months demonstrated both a regrowth of his prostate and a rise in serum PSA levels to pretreatment levels four months post-discontinuation of treatment. We conclude that treatment with a GnRH analogue caused reversible involution of prostatic epithelial cells with parallel effects on serum PSA levels. Consideration of the initial prostate size together with the serum PSA levels can help predict the response to medical castration in men with BPH.