Objective: To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies. Design: Prospective controlled study. Setting: The Egyptian IVF-ET Center, Cairo, Egypt. Patient(s): Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally. Intervention(s): ICSI and karyotyping. Main Outcome Measure(s): Abnormal karyotype. Result(s): Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and I had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P < .001). Conclusion(s): ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies. (C) 2001 by American Society for Reproductive Medicine.