Background: High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom-and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age-and sex-matched controls without any history of DHRs. Method: Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Results: Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) lg/l vs. 2.8 (1.6-4.3) lg/l vs. 2.6 (1.8-3.6) lg/l, respectively, (p >0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) lg/l, mild anaphylaxis 3.0 (1.9-4.9) lg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) lg/l were also comparable (p >0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. Conclusion: The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.