The problem of unexplained male infertility was investigated by electron microscopic study of spermatozoa from 51 males. The subjects were subdivided as follows: group A (n = 25) normal fertile males (controls), group B (n = 13) successful in-vitro fertilization (IVF) cases (fertilization rate >50%), group C (n = 13) failed IVF cases, All subjects included in groups B and C had a 6-12 year history of childlessness and IVF was employed when other methods of assisted reproduction failed, The study of spermatozoa in fertile males (controls) was carried out to establish baseline ultrastructural abnormalities, In all 51 cases, an average of 330 (280-800) sperm heads and 660 (330-190) sperm tails were studied, Decondensation of nuclear chromatin was observed in 70 +/- 15% (mean +/- SD) of spermatozoa in failed IVF cases, 16 +/- 5% in successful IVF cases and 7 +/- 3% in controls, These results were found to be statistically significant (P > 0.001), The mean value for motility of spermatozoa in all three groups was within accepted limits of normality, It is concluded that decondensation of nuclear chromatin seen by electron microscopy is one of the most important causes of male infertility, It is advocated that electron microscopic examination of semen should be carried out in all cases of longstanding, unexplained male infertility before embarking upon IVF programmes.