The distribution of total fibrinolytic activity in seminal plasma, as well as specific tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor (PAI), has been studied using antigen and activity techniques in 170 ejaculates of men attending for assessment because of infertility without genital urinary pathology. Among these 170 patients, 18 showed oligoasthenoteratospermia, 28 showed azoospermia, and 124 showed normozoospermia. The seminal values were 50 times higher (262 to 289 ng/mL in antigen and 179 to 199 x 10 (3) IU/L for activity) than values in blood for t-PA and 15 times higher than values in blood for u-PA (18.4 to 26 ng/mL and 1.5 to 2.4 IU/mL, respectively). There was no correlation between the two levels in antigen or activity, but a higher concentration was observed in all first fractions from split ejaculates measurements. Moreover, t-PA was significantly lower in semen with abnormal liquefaction compared with semen exhibiting normal liquefaction. Zymography confirms the active forms. PAI was absent or at the detection limit for normozoospermia, whereas patients with oligoasthenoteratospermia or azoospermia showed high PAI antigen and activity levels. These data demonstrate that seminal PA activity may be related to sperm fertilizing capacity.