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In this study we determined the frequency, sensitivity and specificity of anti cyclic citrullinated peptides (ANTI-CCP) IgG antibody, total RHEUMATOID FACTOR (RF-T), and RF isotypes in Iranian patients with RHEUMATOID ARTHRITIS (RA) and their association with age, clinical and serological parameters. ANTI-CCP and RF-T and RF isotypes level were measured in 418 patients and 399 healthy controls by enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-REACTIVE PROTEIN (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and DISEASE ACTIVITY score (DAS28) were evaluated in RA patients. The ANTI-CCP was positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was 61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and 21.9% were positive for all three RF classes. The ANTI-CCP positive patients showed increased number of swollen joints. On the other hand, RF-T positive patients exhibited a longer disease duration, lower age of onset and also higher ESR, CRP level and increased swollen joints. RF-T titer was significantly higher in RA patients with active disease compared to remission, low and moderate active groups. The sensitivity and specificity were 53.1, 95.3 for ANTI-CCP antibody and 61.8, 82.3 for RF-T. Our results support that ANTI-CCP and RF titer maybe valuable in estimation of DISEASE ACTIVITY and other inflammatory parameters in RA patients.