During the past 3 years we have used direct injection of spermatozoa into the cytoplasm of the oocyte (DISCO) in an attempt to procure conception in vitro where subzonal insemination (SUZI) has failed. Acknowledging the paucity of information about this invasive procedure in humans, it was clearly the only alternative for some patients. A total of 58 patients (cycles) who had had previously failed SUZI elected for this approach. Sibling oocytes, where possible, were used as a comparison between DISCO, SUZI, partial zona dissection (PZD) and microdrop in-vitro fertilization (IVF). Fertilization and embryo transfer was achieved by 66% (n = 38) of patients. Patients with embryos derived solely from DISCO (n = 19) produced four clinical pregnancies (21%), four patients had embryo transfer from SUZI embryos only with no pregnancies, and 15 had embryo transfer from a mixture of SUZI and DISCO embryos, with one dizygotic twin pregnancy from a combined SUZI and DISCO embryo transfer (7%). Twins, one male and one female, have been delivered, there has been one miscarriage and two pregnancies are ongoing. Of the 627 oocytes, 251 were used for DISCO and 71 (28%) were fertilized, 296 were used for SUZI and 29 (10%) were fertilized; 70 were used for PZD, two (3%) were fertilized, and none of the 10 undergoing microdrop IVF were fertilized. Of the 58 patients (cycles) 31% (n = 19) had fertilization with DISCO only, 8% (n = 4) with SUZI only, 28% (n = 15) with both SUZI and DISCO, while only one (2%) had fertilization with PZD.(ABSTRACT TRUNCATED AT 250 WORDS)