In a study group of 166 patients with unusually high maternal serum alpha-fetoprotein values greater than or equal to 5 multiples of the median, 110 (66%) patients had a condition affecting obstetric care compared with 14% in the 2.5 to 2.9 range, 26% in the 3.0 to 3.9 range, and 30% in the 4 to 4.9 range of multiples of median. Fetal anomalies composed a significantly greater proportion (p less than 0.0001) of positive findings in the study group than the group with maternal serum alpha-fetoprotein values of greater than or equal to 2.5 to 4.9 multiples of the median. Fetal death either before 20 weeks or of one twin occurred significantly more often in the study group (p less than 0.0001). Neural tube defects (21%) and fetal death before 20 weeks (19%) were the most common findings in the study group. There was not a statistically significant difference (p less than 0.53) in pregnancy complications or in late complications between the two groups although oligohydramnios and abdominal pregnancies occurred more often in the study group (p less than 0.029 and less than 0.011). Diagnosticians evaluating patients with unusually elevated maternal serum alpha-fetoprotein values must be aware of the usual differential diagnosis as well as rarer causes. One must recognize that finding an unaffected fetus does not preclude the subsequent development of a pregnancy complication.