Background: Lofgren's syndrome is commonly regarded as a distinct clinical entity. Methods: We have in detail evaluated a large group of patients (n=150) with an acute onset of sarcoidosis with bilateral hilar lymphadenopathy (BHL), in most with cases fever, erythema nodosum (EN) and/or bilateral ankle arthritis or periarticular inflammation. Within this group, 87 patients had EN (EN pos), while 63 were without EN (EN neg) though with distinct symmetrical ankle inflammation. Results: EN pos and EN neg patients were identical in every aspect except that there were significantly more women in the EN pos group, 58 women (67%), compared to only 17 (27%) women in the EN neg group (p<0.0001). In all other aspects such as age, smoking habits, seasonal clustering of disease onset, rate of positive biopsies, chest radiography, pulmonary function, bronchoalveolar lavage (BAL) cell distributions including the typically increased CD4/CD8 ratio, and clinical development of the disease, the EN pos and EN neg groups were close to identical. The two groups were also identically strongly associated with HLA-DRB1* 0301/DQB1*0201, with 60 (69.0 %) and 44 (69.8 %) having this particular HLA type in the EN pos and EN neg groups, respectively. Such patients recovered to the same degree, i.e. at almost 100 %. Conclusions: We conclude that manifestations of Lofgren's syndrome differ between men and women, with EN found predominantly in women while a marked periarticular inflammation of the ankles or ankle arthritis without EN is seen preferentially in men.