In this study, we investigated clinical features, aetiology, prospective follow-up results and also factors favouring secondary erythema nodosum (EN) in patients with EN. A total of 50 patients (mean age 38 y) with a diagnosis of EN between 1993 and 2002 in our clinic were included in the study prospectively. A biopsy was performed in 30 of the patients. Patients were considered to have secondary EN when an underlying condition was found, and to have primary (or idiopathic) EN when no such condition was found. For the diagnosis of the underlying diseases, diagnostic criteria and/or diagnostic methods were used. Categorical variables were compared by using chi(2) test. The majority of the patients were female (6F/1M) and 54% of cases had a determined aetiology. The foremost aetiology was primary tuberculosis (18%) followed in decreasing order by a poststreptococcal (16%), sarcoidosis (12%), inflammatory bowel diseases (IBD) (4%), Behcet's disease (2%), and pregnancy (2%). All the patients were followed for a mean duration of 7 y. The nodosities relapsed every y in 74% of idiopathic EN patients but in only 1 (Behcet's disease) of the secondary ones. Factors favouring secondary EN were as follows: prolonged fever, cough, sore throat, not relapsing EN, abnormal chest X-ray, leukocytosis, an erythrocyte sedimentation rate of higher than 50 mm/h and a CRP value of higher than 6 times the upper limit of normal. All the patients had bed rest and the majority was given naproxen. The outcomes were usually favourable within 7 d. The patients with an underlying disease were given specific treatment. EN has been associated with numerous diseases. In order to reduce cost and duration of diagnosis, every centre should determine its own most frequent aetiological factors. Factors favouring secondary EN should also be determined. Our study revealed primary tuberculosis, streptococcal pharyngitis, sarcoidosis, IBD, and Behcet's syndrome as the main aetiologies of EN.