• Mean whole blood serotonin (5-HT) levels were elevated in groups of autistic and severely retarded children. Eight of 27 (30%) individual autistic children, 13 of 25 (52%) severely retarded children, two of 23 (9%) mildly retarded children, and none of the control children had statistically significant blood 5HT levels elevations (hyperserotonemia). Hyperserotonemic autistic children excreted more urinary 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptamine, and vanillylmandelic acid than did mildly retarded children with normal blood 5-HT levels. Rates of depletion and repletion of blood 5-HT levels in these two groups following reserpine therapy were identical. Oral tryptophan administration doubled urinary 5-HIAA excretion in both groups and raised urinary 5-HT levels in hyperserotonemic autistic children, but lowered urinary 5-HT in mildly retarded, normal blood 5-HT children. No clear mechanism for hyperserotonemia was found; the rationale for further investigations is discussed.