Most urologists' clinical experience is that infertility is a rare presenting sign of life-threatening medical disorders in men. Considering the current practice of infertile couples presenting to the gynecologist for initial evaluation and the popularity of assisted reproductive technology, many men are evaluated with a semen analysis alone and treatment instituted without urologic consultation. This may cause a delay in the diagnosis of a significant medical illness or misdiagnosis of a potentially treatable cause of male factor infertility. We reviewed the records of 1236 new male infertility patients presenting to Bowman Gray School of Medicine and Baylor Medical College in an attempt to determine the frequency of significant medical disease in men presenting with infertility and whether any pattern of semen analysis findings was predictive of these disorders. Thirteen men, or 1.1% of the total population, were found to have a significant medical illness upon full urologic evaluation (Table 5). Testicular tumors were found in six, spinal cord tumor in one, brain tumors in three, genitourinary malformation in two, and a chromosomal abnormality in one. Interestingly, one of these patients was a physician with bilateral testicular cancer who had an abnormal semen analysis and had undergone multiple cycles of intrauterine insemination before referral. We could not identify a pathognomonic pattern on semen analysis that would allow us to predict the presence of medical illnesses in these 13 patients. Sperm counts ranged from azoospermic to almost normal semen parameters.(ABSTRACT TRUNCATED AT 250 WORDS)