Beta-lactam antibiotics (BLAs) can provoke drug hypersensitivity reactions, particularly delayed-type reactions. This article presents a case of drug allergy with manifestations of Stevens-Johnson syndrome (SJD) in a 42-year-old man with yersiniosis and active herpesvirus -4, -6 type, who received amoxacillin with clavulanic acid. The patient underwent a basophil activation test (BAT) for BLAs, and a positive result was found for both amoxacillin and 2nd and 3rd generation cephalosporins. On the example of a clinical case, probable pathogenetic mechanisms of the risk of the appearance of immediate-type hypersensitivity reactions in persons with active herpesvirus -4, -6 type infection are shown. The possibility of using the cellular BAT for the diagnosis of delayed-type hypersensitivity reactions and for the diagnosis of cross-reactions to antibiotics has also been demonstrated.