Institutionalized epileptic patients on long-term anticonvulsant diphenylhydantoin (DPH) therapy were examined clinically. DPH plasma levels were unexpectedly high in 54% despite rather poor seizure control. No patient was free from side effects, which included gingival hypertrophy (90% of patients), increased alkaline phosphatase activity (55%), suggestion of a sensory peripheral neuropathy (34%), central nervous system (CNS) intoxication (22%), coarsened facial features (19%), tendency to bleed excessively (15%), hirsutism (12%), and mild megalocytic anemia (5%). CNS intoxication correlated with high plasma DPH levels, reports of deteriorating behavioral and motor performance, and the findings of nystagmus on vertical gaze or truncal ataxia, though not all patients with high plasma levels were clinically intoxicated. Alarming were the often disfiguring changes of gums and facial structures and the tendency to develop signs of vitamin D deficiency secondary to therapy. Hirsutism was rare in black patients. Plasma DPH level determinations are recommended as part of the management of mentally retarded epileptic patients but do not replace clinical acumen and skill.