A random sample of 1000 subjects (20-65 years of age) received a postal questionnaire regarding sick building syndrome (SBS), including the three-dimensional model of demand-control-support (DCS). The response rate was 70% (n = 695), and 532 were occupationally active. Female gender and atopy were the main predictors of symptoms. Eye symptoms were more common at low social support combined with strained work situation [odds ratio (OR) 2.37], and at high social support combined with active work situation (OR 3.00). Throat symptoms were more common at low social support combined with either passive (OR 1.86) or strained situation (OR 2.42). Tiredness was more common at low social support combined with either passive (OR 2.41), strained (OR 2.25), or active situation (OR 1.87), and at high social support combined with active work situation (OR 1.83). Low social support combined with either passive (P = 0.01) or strained job situation (P = 0.01) was associated with a higher symptom score (SC). The lowest SC was found at a relaxed work situation, irrespective of social support. In conclusion, female gender, low age, asthma, atopy and psychosocial work environment are associated with symptoms. The three-dimensional model can predict symptoms compatible with SBS, but in a more complex way than earlier research indicated. Practical Implications A multi-disciplinary approach, including psychosocial stress factors as well as personal factors such as gender, age, atopy and asthma, and indoor exposures, should be applied in studies on symptoms compatible with sick building syndrome (SBS). Males and females perceive psychosocial work conditions differently, and may react differently to job stressors. The psychosocial work environment can be as important as gender and atopy as a predictor of SBS symptoms.