Background. The spectrum of interferon-beta (IFN-beta)-associated nephropathy remains poorly described and the potential features of this uncommon association remain to be determined. Methods. In this study we retrospectively analysed the clinical, laboratory, histological and therapeutic data of patients with biopsy-proven renal disease in a context of IFN-beta treatment administered for at least 6months. Results. Eighteen patients (13 women, median age 48years) with biopsy-proven renal disease occurring during IFN-beta therapy were included. The median exposure to IFN-beta (14 patients were treated with IFN-beta1a and 4 patients with IFN-beta1b) was 67months (range 23-165months). The clinical presentation consists in hypertension (HT; 83%), malignant HT (44%), proteinuria (protU) >1g/g (94%), reduced renal function (78%), biological hallmark suggesting thrombotic microangiopathy (TMA; 61%), oedematous syndrome (17%) or nephritic syndrome (11%). The pathological findings included typical features of isolated TMAs in 11 cases, isolated focal segmental glomerulosclerosis (FSGS) lesions in 2 cases and 5 cases with concomitant TMA and FSGS lesions. An exploration of the alternative complement pathway performed in 10 cases (63%) did not identify mutations in genes that regulate the complement system. The statistical analysis highlighted that the occurrence of IFN-beta-associated TMA was significantly associated with Rebif, with a weekly dose >50mg and with multiple weekly injections. In all cases, IFN-beta therapy was discontinued. Patients with TMA lesions received other therapies, including corticosteroids (44%), eculizumab (13%) and plasma exchanges (25%). At the end of a 36-month median follow-up, persistent HT and persistent protU were observed in 61% and 22% of patients, respectively. Estimated glomerular filtration rate <60mL/min/1.73m.sup.2 was present in 61% of patients. Conclusions. IFN-beta-associated nephropathy must be sought in the case of HT and/or protU onset during treatment. When TMA and/or FSGS are observed on renal biopsy, early discontinuation of IFN-beta is essential.