To determine whether maternal HIV infection is associated with altered fetal cardiac structure and function, echocardiography was performed at 5 centers in 174 fetuses of HIV-infected mothers (FHIM) (mean gestational age = 32.9, SD = 3.7 wks). Studies were analyzed by a single reviewer blinded to gestational age. Noncardiac and cardiac measurements from 2D images and Doppler velocities through AV and semilunar valves and the umbilical artery were converted to Z-scores based on published normal data. FHIM had increased LV and RV end-diastolic wall thickness and reduced LV enddiastolic dimension (p < 0.001) compared to normal controls. Peak AV and semilunar valve velocities, mitral and tricuspid peak N/E velocity ratios (A = atrial systole, E = early ventricular diastole), and umbilical artery systolic/ diastolic velocity ratios were higher in FHIM (p < 0.05). Heart rates, however, were slower in FHIM ( < 0.001). RV diastolic dimension and femur length also tended to be smaller in the HIV+ group, but were not statistically different between the groups. When 22 FHIM with postnatally confirmed HIV infection (HIV+) were compared to 123 uninfected FHIM, LV diastolic dimension (p = 0.019) was smaller in the HIV+group. Other 2D measurements and Doppler velocities did not differ for the two groups. When maternal factors were analyzed, a correlation existed between maternal hemoglobin and fetal LV end-diastolic dimension. Cardiovascular changes in FHIM suggest a state of increased placental vascula r resistance and reduced ventricular compliance. Vertically transmitted HIV infection may be associated with altered ventricular size in utero but does not appear to alter fetal cardiac function. The observed changes may be secondary to maternal factors.