Fifteen infants with moderate to severe congenital renal disease were prospectively studied by serial renal, neurodevelopmental, neurophysiologic, and anthropometric assessments. The observation period ranged from 3 to 25 months (mean = 10.9). Eight patients maintained a Mental Development Index (MDI) above the 16th percentile (greater than -1 SD) and comprised group 1. Of the remaining seven patients (group 2), three had an MDI less than 16th percentile when first studied and four had serial decreases of the MDI to less than 16th percentile. Although motor development was more delayed in group 2 at study entry, there were no significant changes of motor performance levels for either group during the study period. Group 2 patients had smaller length (p less than 0.05) and head circumference (p less than 0.05) standard deviation scores in comparison with group 1, and they had higher serum creatinine values (mean = 3.8 vs 1.3 mg/dl, respectively; p less than 0.01). By spectral electroencephalography, the expected progressive increase of the frequency of cerebral cortical background activity with age was demonstrated in group 1 but was not seen in group 2 (multivariate analysis of variance p less than 0.03). This increase of faster-frequency activity was primarily manifested in the left cerebral hemisphere of group 1 patients (p less than 0.01), a finding that was also absent in group 2. The frequent occurrence of neurodevelopmental abnormalities in infants with renal failure is possibly a consequence of impaired dominant hemispheric maturation in the first several years of life, which is clinically manifested as deterioration of cognitive function.