Rheumatoid arthritis is an inflammatory joint disease, affecting 1% of people worldwide. Genetic and enviromental factors play an important role in rheumatoid arthritis, where the etiopathology is still unkown. The clinical course ranges from mild joint swelling to severe polyarthritis. Matrix metalloproteinases are proteolytic enzymes and mediate the destruction of proteoglycanes, collagens in cartilage and bone matrix. In the present study, functional relevant promoter polymorphisms of MMP-1 1G/2G, MMP-1 A/T, MMP-1 C/T and MMP-3 5A/6A were genotyped in 308 patients and in 110 controls, to test whether the polymorphisms contribute to the severity of the disease. A strong linkage disequilibrium was observed between the MMP-1 1G/2G and the MMP-3 5A/6A polymorphisms. The degree of radiographic joint destruction correlated significantly with the 1G-5A haplotype and duration of disease. This association was phasic, indicating that possession of the 1G-5A haplotype has a protective effect over a period of about 15 years of RA. The correlation of SE with the Ratingen score was comparable. Results of the promotor polymorphism show a significant association of the 2G allel and the progression of disease in the first 15 years. Similar results were also found with the 1G allele of MMP1 alone and with the duration of disease after 15 years. MMP-3 5A/6A-, MMP-1 C/T and the MMP-1 A/T- polymorphisms show no association with the progression of disease in RA.