Study Objective. To determine the relative bioavailability of lamotrigine (LTG) chewable dispersible tablets after rectal administration. Design. Two-period, crossover study with a 2-week washout between dosing periods. Setting. Clinical research center. Patients. Twelve healthy adult volunteers. Intervention. One hundred milligrams of a LTG chewable dispersible tablet was administered by oral and rectal routes. Measurements and Main Results. Plasma samples were collected before and up to 120 hours after drug administration. The samples were analyzed for LTG by high-performance liquid chromatography, and the relative bioavailability was determined. Drug concentrations were lower after rectal than after oral administration. The relative bioavailability (F = AUCrectal/AUCoral) was 0.52 ± 0.23 (SD). Conclusion. Drug prepared from LTG chewable dispersible tablets is absorbed rectally, although not to the same extent as when given orally. Rectal administration of suspension of these tablets can be an acceptable route of administration.