Intracytoplasmic sperm injection (ICSI) has been successful in cases of extreme oligoasthenozoospermia in achieving pregnancies via in-vitro fertilization (IVF) with the lowest imaginable sperm counts. In azoospermia caused by congenital bilateral absence of the vas deferens (CBAVD), it has been shown that epididymal spermatozoa can be retrieved in large numbers, but fertilization rates using conventional IVF are low. Furthermore, no fertilization has ever been possible using testicular spermatozoa with conventional IVF. In the most extreme case of absence of the epididymis, spermatozoa can only be retrieved from macerated testicular biopsy specimens. In such cases, all that can be seen are free-floating Sertoli cells with many spermatids attached, and only occasional spermatozoa per high power field which have only the barest, occasional, slightly twitching motion. The objective of the present study was to determine whether ICSI could achieve better results than conventional IVF with microsurgical aspiration of spermatozoa (MESA). ICSI (using epididymal or testicular spermatozoa) from men with CBAVD or irreparable obstructive azoospermia, achieved good fertilization and normal embryos in 82% of cases, compared to 19% with conventional IVF. There was an overall fertilization rate of 45%, with 85% progressing to normally cleaving embryos using ICSI, compared to 6.9% using conventional IVF. The pregnancy rate with ICSI/MESA was 47% per stimulated cycle (normal delivery rate was 30%), compared to 4.5% with conventional IVF. These results were achieved in patients who had consistently failed to fertilize in previous cycles with MESA and conventional IVF.(ABSTRACT TRUNCATED AT 250 WORDS)