Felbamate is a new antiepileptic drug (AED) with a good safety profile. Anorexia has been reported in patients taking felbamate, but the incidence and severity of this side effect have not been adequately investigated. We studied 65 patients with intractable seizures who received adjunctive felbamate therapy as part of clinical research trials or in a compassionate-use program. Mean treatment time on felbamate was 23 weeks (+/- SD 16; range, 6-116 weeks). Forty-nine patients (75%) lost weight during the trials. For subjects older than 15 years, there was a mean weight loss of 3.17 kg or 4.11% of body weight (T = 191.5, z = 4.18, p < 0.001). For subjects 15 years or younger there was a mean weight loss 0.20 kg or a loss of 1.77% of body weight (T = 52.5, NS). Twenty-two patients (34%) lost > 4 kg, and seven patients (11%) lost > 8 kg. Adjunctive treatment of adults with severe epilepsy with felbamate may be associated with clinically significant weight loss.