Down syndrome or trisomy 21 can be caused by three types of chromosomal abnormalities: free trisomy 21, translocation or mosaicism. The cytogenetic diagnosis, made through karyotypic examination, is important mainly to determine recurrence risks to assist genetic counselling. The object of this work was to carry out a cytogenetic profile of confirmed cases of Down syndrome seen in the General Genetics Outpatient Service in a teaching hospital--Hospital de Base in Sao Jose do Rio Preto--from the implementation of the service in 1973 to November 2005, with the purpose of establishing the nature of the cytogenetic abnormalities of these patients. A retrospective study was performed, in which the karyotypes of patients with Down syndrome consulted at the General Genetics Outpatient Service of HB-FAMERP from 1973 to November 2005 were investigated. The results of cytogenetic analysis were obtained from the consultation register and patients' hospital records. The results show 387 Down syndrome cases confirmed by karyotypic examinations. Of these, 357 (92.2%) patients had free trisomy of chromosome 21, 24 (6.2%) had translocation involving chromosome 21 and 6 (1.5%) had mosaicism. Nondisjunction was the main cause of Down syndrome, as the majority of the patients have free trisomy of chromosome 21. The cytogenetic pattern of Down syndrome is variable among different studies. (Contains 1 figure.)