AIMS: In nodular sclerosing Hodgkin's disease (NSHD), the prognostic relevance of the histopathological grading in two subtypes NSI (low-grade) and NSII (high-grade) remains controversial. Analysis of follicular dendritic cells (FDC) may provide new prognostic parameters. METHODS AND RESULTS: Tumours from 59 patients with NSHD were studied. Mean follow-up time was 8 years. Forty-one cases were classified as NSI and 18 as NSII. FDC were immunostained with the paraffin-resistant monoclonal antibodies CD21 and CNA.42. We distinguished three patterns in the neoplastic tissue: FDC1, the presence of well-defined follicle-like structures (n = 20); FDC2, the presence of largely destroyed FDC networks (n = 25); and FDC3, no or a few isolated FDC (n = 14). The three groups differed clearly regarding the frequency of relapse and the survival. The longest survival was seen in the FDC1 group, the shortest in the FDC3 group, the FDC2 group being intermediate (P = 0.0025). FDC status was a discriminating prognostic factor for all patients, and within various age and stage categories. Combining the FDC status and the NSI-NSII grading defined the best survival group as FDC1-NSI. CONCLUSIONS: Assessment of FDC pattern, associated with histological subtyping, brings valuable data for predicting survival and outcome in NSHD