Standardization of the histopathological assessment of synovial membrane specimens might facilitate the diagnosis of chronic rheumatic and non-rheumatic joint diseases. We would like to propose a histological graduation scheme ("synovialitis score"), which is applicable to all forms of synovitis, irrespective of its etiology. This score evaluates the three compartments of chronic synovialitis [enlargement of lining cell layer, activation of synovial stroma (i. e. resident cells), leukocytic infiltrate] semiquantitatively (from 0=absent to 3=strong). Each compartment is graded separately, and the sum resembles the synovialitis score, which is interpreted as follows: 0-1: no synovialitis, 2- 3: slight synovialitis, 4-6: moderate synovialitis, 7-9: strong synovialitis (for sample photos see also www.charite.de/ch/patho/Webpage/pages/forschung/arbeitsgruppen/ag-krenn/index.htm). A total of 483 synovial specimens (resections n=462, biopsies n=21) were graded by two independent observers. Clinical diagnoses were osteoarthrosis (OA; n=153), posttraumatic arthritis (PtA; n=31), rheumatoid arthritis (RA; n=239), psoriatic arthritis (PsA; n=32), reactive arthritis (ReA; n=7), and controls (Co, n=21) from necropsies of patients without joint damage. The correlation between two observers was high (p<0.001). The correlation coefficient between the different samples from the same joint in n=112 cases was between 0.86 and 0.95. Median synovialitis scores when correlated with clinical diagnoses were: Co 0.5, OA 2, PtA 3, PsA 3, ReA 4, RA 5. The differences in scores between Co and all other groups were highly significant (p<0.001). A synovialitis score of 4 points and more was strongly associated with rheumatic joint diseases (sensitivity 73%, specificity 86%). Validation of the synovialitis score by gene expression data showed good correlations for the lining cell enlargement with MMP1 (0.685), for the leukocytic infiltrate with CD3 (0.754) and CD138 (0.744) and for the stroma activation with CD14 (0.744). The proposed synovialitis score is based on well definable histopathologic criteria and contributes to the diagnosis of rheumatic and non-rheumatic joint diseases.