We have conducted a prospective study to ascertain the reliability of the triple test in detecting aneuploid fetuses in a Mediterranean, pregnant population. 2978 singleton pregnancies in the 15-22 completed week's gestational range were enrolled in this study between January 1992 and June 1994. The measurements of the analytes AFP, hCG and UE3 in the maternal serum combined with maternal age in a multivariate risk approach were utilized to detect pregnancies at increased risk (cut of > or = 1:270) to undergo prenatal diagnosis by amniocentesis. This screening was preferentially reserved to young patients (median age of the population 29 years). 212 pregnancies resulted screen positive to triple test and 178 accepted fetal chromosomal analysis. Three Down's syndrome, a Turner 45XO and a triploidy 69XXY were detected in the sample undergoing prenatal diagnosis. One aneuploid pregnancy (Down's syndrome) was recorded in the population with negative result (risk < 1:270). As part of this study we have subsequently compared the sensitivity of the test substituting total hCG with free-beta marker in samples from aneuploid pregnancies (16 cases) and unaffected pregnancies (300 cases). The detection rate for the two combinations was identical (81%) as well as the false positive rate (5.7% versus 5.3%) derived from the normal samples. All together these combined results of our study support the increasing call for triple test in screening programmes and indicate that further data be collected before recommending the replacement of total hCG with free-beta analyte.