Blood safety remains an issue of major concern in transfusion medicine in developing countries where national blood transfusion services and policies, appropriate infrastructure, trained personnel and financial resources are lacking. This is aggravated by the predominance of family and replacement, rather than regular benevolent, nonremunerated donors. Thus, in order to identify and encourage healthy, regular and benevolent nonremunerated donors, consenting first-time blood donors in the Yaoundé University Teaching Hospital were screened for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), hepatitis C virus (HCV), human T-cell lymphotropic virus-I (HTLV-I) and syphilis using standard methods. Of 252 first-time donors recruited, 66 (26.2%) were positive for at least one of the infections screened. There were 7.9% positive for HIV, 10.7% for HBSAg, 4.8% for HCV and 9.1 and 1.6%, respectively, for syphilis and HTLV-I. About 30% of the 66 infected persons had co-infections. HIV-positive donors had a significantly increased risk of being positive for antibodies to syphilis (OR = 7.27; 95% CI = 2.23-23.51; P = 0.0007), not observed for HBV, HCV and HTLV-I. These results suggest that blood transfusion is still very unsafe in this community and that it is imperative that emphasis be laid on donor education. Furthermore, donors with a history of sexually transmitted infections should be totally excluded from all donations.