Lactate dehydrogenase C4 (LDH-C4) is the specific isozyme of LDH produced by germ cells. We measured LDH-C4 activity in seminal plasma from infertile men with oligozoospermia or azoospermia using gel electrophoresis. Total LDH activity in seminal plasma from infertile patients (n = 99) was 2,487 +/- 1,384 IU/l (mean +/- SD). LDH-C4 isozyme activity was detected in 63 out of 75 seminal plasma samples from infertile patients with a mean of 383 +/- 356 IU/l (13.8 +/- 8.6% of total LDH). Sperm count was positively correlated with LDH-C4 (r = 0.298; P < 0.05), but not with any other LDH isozymes or with total LDH. Seminal LDH-C4 was significantly lower in patients with varicoceles (253 +/- 223 IU/l) than without varicoceles (474 +/- 262 IU/l). Six azoospermia patients were treated with hCG and hMG. Three out of four patients whose seminal plasma revealed LDH-C4 activity responded to the treatment, whereas none of the other two patients without seminal LDH-C4 activity did. These results indicate the clinical usefulness of seminal LDH-C4 as a potential marker for seminal epithelium activity in the diagnosis and treatment of male infertility.