Circumsporozoite (CS) antibodies, indicating plasmodial infection but not necessarily development of disease, have been shown to be reliable indicators of transmission in endemic areas. To estimate the actual rate of plasmodial infection, the prevalence of CS antibodies was investigated by an ELISA test system in a selected population of 2,131 travelers returning from areas endemic for malaria who presented to an outpatient clinic without any apparent symptom or clinical sign of malaria. Serum specimens from 104 of the investigated 2,131 patients (4.9%) were found to be positive (titer > or = 6.25 international ELISA units [IEU]). The geometric mean titer of antibody concentrations (IEU) in seropositive patients was 18.64 IEU (95% confidence interval [CI] = 13.15-24.13), while it was 2.1 IEU (95% CI = 1.8-2.4) in seronegative patients. A significantly above average risk for plasmodial infection could be found among travelers to East Africa (risk ratio [RR] = 4.5, P < 0.001), West Africa (RR = 4.5, P < 0.001), and Southern Africa (RR = 3.2, P = 0.015), while areas with a comparatively low risk included Central America (RR = 0.86, P < 0.001), the Indian subcontinent (RR = 0.45, P = 0.015), South America (RR = 0.49, P = 0.091), East Asia (RR = 0.68, P = 0.441), West Asia (RR = 0.24, P = 0.099), and Southeast Asia (RR = 0.69, P = 0.094). The results of this study emphasize the importance of adequate malaria chemoprophylaxis in nonimmune travelers to endemic areas. By use of the described method, estimates of the true infection rate of malaria in travelers can be derived for certain areas and the value of prophylactic measures can be demonstrated.