Juvenile myoclonic epilepsy is a comparatively benign form of idiopathic generalised epilepsy. Little is known about the prevalence of difficult to treat or drug resistant patients. Among 155 consecutive patients with newly diagnosed juvenile myoclonic epilepsy evaluated between 1981 and 1998 and followed up for at least 1 year (61 men, 94 women; aged 15-70 years, mean 33 (SD 10.3); onset of juvenile myoclonic epilepsy at the age of 14.5 (SD 3.7), range 6-26; follow up 1-52 years, mean 13.5 (SD 9.9)), there were 15 pseudoresistant patients (9.7%: lack of compliance (eight), insufficient treatment (three), abnormal lifestyle (four)) and 24 patients (15.5%) who had persisting seizures despite adequate therapy and lifestyle. Clinical features associated with drug resistance were (1) the presence of psychiatric problems (58.3% v 19%; chi(2) p<0.001) and (2) independently, the combination of seizure types (Fischer's exact 2 by 4, p=0.0026). Three types were present in 62.5% of resistant patients versus 23.3% in non-resistant patients (chi(2), p=0.0001). None of the resistant patients had myoclonic jerks as the only seizure type or a combination of absences and myoclonic jerks. Family history of epilepsy, age at onset of seizures, sex, presence of photoparoxysmal response, results of conventional neuroimagings (CT and MRI), and delayed diagnosis were not significantly associated with drug resistance. There is thus a significant subgroup of patients with juvenile myoclonic epilepsy who pose difficult therapeutic problems, and the prevalence of resistant cases may be increased in the experience of a referral epilepsy centre.