Two patients with HIV disease developed a pruritic, maculo-papular rash shortly after introducing an association of 2 protease inhibitors (PI) lopinavir/ritonavir (Kaletra). The dermatitis started respectively 7 and 10 days after taking Kaletra, improved on withdrawal, and relapsed following its reintroduction. Although itchy, the dermatitis was not life-threatening, and the patients were treated "through the rash" without suspending the drug. Histopathologic examination of lesional skin showed a non-specific inflammatory infiltration consisting of neutrophils and lymphocytes, but there were no eosinophils, nor dilatation of capillaries in the papillary dermis. HIV positive patients are more prone to drug-related rashes than the general population. Awareness of the side-effects of PI plays an important role in keeping compliance with the treatment and helps patients reach their goal in controlling the development of HIV. The safety profile of Kaletra and its cutaneous side effects have yet to be completely elucidated.