In order to evaluate the safety of the intracytoplasmic sperm injection (ICSI) procedure, a prospective follow-up study of 423 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Before starting the infertility treatment, couples were asked to participate in a follow-up study including genetic counselling and prenatal diagnosis. The follow-up study of the child was based on a visit to the paediatrician-geneticist at birth or at 2 months of age, at 1 year and at 2 years of age when a physical examination for major and minor malformations and a psychomotoric evaluation were done. Between April 1991 and September 1994, 320 pregnancies obtained after ICSI led to the birth of 423 children (222 singletons, 186 twins and 15 triplets). Prenatal diagnosis determined a total of 293 karyotypes, one of which was abnormal (0.3%), and four were benign familial structural aberrations, all inherited from the paternal side. A total of 14 (3.3%) major malformations were observed, defined as those causing functional impairment or requiring surgical correlation. Neurological or developmental problems at the age of 2 months were found in 14 children, four of whom were multiples. Compared to most registers of children born after assisted reproduction and to registers of malformations in the general population, the figure of 3.3% major malformations is within the expected range. Before drawing any firm conclusion, further careful evaluations of the available data are necessary.