Testicular varicocele, the most common cause of male infertility, frequently presents in early adolescence. To determine whether testicular damage occurs early in the natural history of varicocele, testicular biopsy specimens from 13 patients, 13 to 18 years of age (mean age, 15.5 years), were studied. The biopsies were compared with testicular tissue from six normal control subjects 15 to 28 years of age (mean age, 23.2 years). Nine of the patients with varicoceles (69.2%) demonstrated some degree of tubular sclerosis. Ultrastructural study demonstrated that the tubular sclerosis was due to collagen deposition by fibromyocytes in the peritubular sheath. Premature germ cell sloughing was present in greater than 50% of tubules examined in all but one biopsy. Six patients (46%) demonstrated small vessel sclerosis. Quantitation of the germinal epithelium revealed that the mean germ cell/Sertoli cell ratio and the percentage of germ cells present as late stage forms (secondary spermatocytes, spermatids and spermatozoa) were significantly reduced in the varicocele group. The testes of two patients exhibited severe hypospermatogenesis approaching germ cell aplasia. None of these changes were seen in the control group. The authors conclude that pathologic changes in the testes of patients with varicoceles are found at or soon after puberty. The histopathologic features include peritubular sclerosis, small vessel sclerosis, premature germ cell sloughing, and variable degrees of hypospermatogenesis.