PIP: Since 1974, 255 volunteers have been taking part in a clinical trial of gossypol as a male contraceptive agent with the Department of Male Contraceptive Research, Ren Ji Hospital of Shanghai Second Medical University. Among them, 50 people received daily dosages of 20 mg gossypol and 0.5 gm potassium releasing agent. 137 people received daily dosages of 15 mg, 10 received 12.5 mg, and 19 had 10 mg daily. When the contraceptive effects were shown, a weekly maintenance dosage was administered. After 3 months to 8 years of gossypol intake, hypokalemic paralysis occurred in 24 cases. These cases recovered after subsequent treatment with potassium replacement. It was found that all the cases received daily dosages of 15-20 mg of gossypol. When the dosage was reduced to 10-12.5 mg, the hypokalemia did not recur. Some volunteers treated with daily dosages of 20 mg started to have elevated levels of urinary N-acetyl-3-D-glucosaminidase and/or beta-2-microglobulin with simultaneous renal potassium loss after 2 months of gossypol administration. This indicated that gossypol might induce proximal renal tubular damage, which caused the loss of potassium. The results of both animal and clinical trials have shown that the toxicity of gossypol and the recovery of sperm function after stopping use of gossypol was closely related to the dosage of the gossypol intake. It is believed that a decrease in the loading dosage of gossypol might be an approach to avoid the occurrence of hypokalemia and the appropriate dosage with contraceptive effects needs to be identified. It is also believed that the cause of hypokalemia is due to renal tubular damage.