To learn whether patients taking beta-blocker (BB) drugs were at increased risk of having systemic reactions (SRs) from allergen immunotherapy, we prospectively studied 56,105 injection visits in 3178 patients during a 1-year interval. A total of 166 SRs occurred in 144 patients (4.5% of all patients) or 3.0 SRs occurred per 1000 injection visits. Sixty-eight patients were taking BB drugs throughout the year, and only one patient had an SR. By chance, 3.08 patients were expected to have had SRs. We conclude that BB drugs did not increase the frequency of SRs in the patients studied who were receiving immunotherapy (p greater than 0.95). Patients taking BB drugs may still be at increased risk, however, from more severe SRs or their SRs may be more refractory to therapy.