Objective: To document the pathology of five siblings with complete globozoospermia and to report the effectiveness of repeated intracytoplasmic sperm injection (ICSI) treatment as therapy. Design: Case report. Setting: A tertiary center for assisted reproduction. Patients(s): Five siblings with globozoospermia. Intervention(s): Twenty cycles of repeated ICSI treatment. Detailed light and electron microscopy studies were performed on three of the globozoospermic brothers. Main Outcome Measure(s): Clinical pregnancy and live birth after ICSI treatment. Result(s): Light and electron microscopy showed that all spermatozoa had round heads and no acrosome. Of 129 metaphase-II oocytes injected, 49 fertilized normally, giving an overall fertilization rate of 38% (range, 0-100%). No pregnancies resulted from 13 cycles in brothers 1-3. Brothers 4 and 5 had three pregnancies after seven ICSI cycles, with one live birth and two first-trimester losses. Conclusion(s): Despite variable fertilization rates, pregnancies and a live birth can be achieved after repeated ICSI treatment cycles in globozoospermic siblings. No apparent pattern was manifest that reflected the true pathology or determined the outcome of ICSI treatment. (C) 2004 by American Society for Reproductive Medicine.