Administration of nevirapine to HIV-infected injection drug users who also receive methadone results in a significant reduction in methadone exposure after 710 days of therapy. Many patients require an increase in methadone dose to counteract this effect. Eight patients (4 men and 4 women) attending the National Drug Treatment Clinic, Trinity Court (Dublin, Ireland), who were receiving stable daily methadone maintenance therapy, were HIV infected, and fulfilled standard criteria for commencement of antiretroviral therapy were recruited into the study.Pharmacokinetic data show a reduction in AUC for methadone of 57% and 51% and a reduction in maximum concentration of 48% and 36% when it is administered in combination with EFV and NVP, respectively. However, the possibility that a process of "induction-detoxification" occurs during the first 2-3 weeks of therapy indicates that the increase in methadone dose required is not as significant as is suggested by these data. A mean increase in methadone dose of 16%-22% may be required in some, but not all, patients after 7-10 days of antiretroviral therapy.