Thirty-one (31) subfertile men with idiopathic iligozoospermia were treated by a daily oral medication of 600 units of pancreatic kallikrein (Padutin(R) 100) over a period of 3 months. Total sperm output increased significantly with a maximum 3 months after initiation of therapy. In addition, quantitative and qualitative sperm motility improved during treatment and was still improved 2 months after withdrawal of therapy. Compared to other regimens, oral administration of 600 units kallikrein for a period of 3 months yielded better results than shorter medication periods or lower dosage. Quantitative determination of several serum proteins occurring in seminal plasma before, during and after kallikrein therapy showed a significant increase of alpha 1, x-antichymotrypsin. Thus, kallikrein treatment seems to affect, to a certain degree, the secretory activity of the accessory glands or the blood-seminal plasma barrier. Determination of serum gonadotropins and serum testosterone levels showed a significant increase of LH and testosterone during kallikrein treatment, whereas FSH was unaffected. Thus, systemic kallikrein administration induces significant changes of the pituitary-gonadal axis influencing spermatogenesis and epididymal sperm maturation. However, the local action of kinins as pharmacological active tissue hormones has to be considered too.