A patient with suspected isoniazid-induced lupus erythematosus had positive reaction for antinuclear antibody, lupus erythematosus cell, gamma and nongamma direct antiglobulin tests. Severe pericarditis with life-threatening pericardial tamponade required emergency pericardiocentesis. Recurrence of the pericardial effusion with tamponade necessitated use of corticosteroids. We suggest use of steroids early in drug-induced lupus erythematosus, if associated with severe pericarditis with any question of pericardial tamponade (even in the face of underlying tuberculosis).