Immediate-type allergy to natural rubber latex (NRL) is common in highly exposed groups, particularly in health-care workers and patients with spina bifida. The occurrence of NRL allergy was investigated in subjects not belonging to such risk groups. A total of 493 patients presenting with various diseases for allergologic evaluation was studied. A questionnaire-based history was taken, skin prick tests with NRL milk and common aeroallergens were done, and NRL-specific serum IgE antibodies were measured. A total of 317 subjects (64.3%) was atopic. There were skin prick test reactions to NRL in 80 (16.2%) and NRL-specific IgE in the serum in 79 (16.0%) subjects; both were found in 25 patients (5.1%). Altogether, NRL sensitization was found in 134 patients (27.2%). By history and/or challenge tests, 13 subjects (2.6%) were diagnosed as having clinically relevant NRL allergy. In five of these, anaphylactic reactions had occurred during dental procedures, and in four during general anesthesia; 10 subjects reported immediate-type reactions to NRL products in daily life. All patients with clinically relevant NRL allergy had a skin prick test reaction to NRL milk (sensitivity 100%). Nine had specific IgE antibodies in the serum (sensitivity 69.2%); respective specificity was 86.0% or 85.4%. Nine of the 13 patients (69.2%) with NRL allergy were atopic. Despite exclusion of those at risk, many patients had clinically relevant allergy to NRL, and many of these had had severe reactions. NRL allergy is an important health issue also beyond the known risk groups.