Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of NHL. Different chemotherapy regimens tested in the past showed RR of appx 80% with no improvement in prognosis & OS. CHOP regimen has been the standard treatment for these patients (pts). Rituximab has improved response rates & survival in CD20 positive lymphoma pts, especially elderly (GELA trial: CR 73% vs. 63%). We retrospectively evaluated pts of DLBCL treated with R-CHOP regimen between April 2001 & June 2005. All pts had biopsy and IHC of lymph node/extranodal site, & CT scan of neck, chest, abdomen; BM biopsies; CBC, serum chemistries; 2D echocardiography/MUGA scans. All pts received Rituximab (375mg/m2) & CHOP 3 weekly for a maximum of 8 cycles. Pts who received at least 1 & 3 cycles of R-CHOP were evaluable for toxicity and response respectively. In total, 36 pts were included for analysis. The median age was 53 years, 10/36 pts (27.8%) were >60 years. 25/36 were male (69.4%). ECOG performance status: 0–1 in 30/36, and 2–4 in 6/36. 11/36 had B-symptoms, 16/36 had high LDH, 6/36 had bulky disease. Extranodal involvement was present in 19/36; 10/36 had ≥2 sites of extranodal involvement. Lymph nodal swelling was most common presentation in 24/36 (66.7%), followed by pain 10/36 (27.8%), weight loss 9/36 (25%), fever 7/36 (19.4%), skin nodules 3/36 (8.3%). Extranodal sites were: bone marrow 5/36, bone 4/36, skin 3/36, GIT 3/36, pleural effusion 2/36, lungs 2/36, other soft tissue 2/36, and parotid, nasopharynx, orbit, adrenal, testes, kidneys-1 each. Gallium scan at base line, done in 12/36, was positive in 11 pts (91%). Stage distribution was as follows: stage-I none, stage-II 10/36 (27.8%), stage-III 13/36 (36.1%), stage-IV 13/36 (36.1%). IPI scoring was-low risk 13/36 (36.1), low intermediate 9/36 (25.0%), high intermediate 13/36 (36.1) & high risk 1/36 (2.8%). A total of 199 cycles of R-CHOP were administered with a median of 6 cycles per patient. Of the 33 pts evaluable for response, 22 achieved CR (66.7%), 9 PR (27.3%), 1 each SD & PD. There were 2 treatment related mortalities. Toxicities were: grade III/IV neutropenia in 12/36 (33.3%), thrombocytopenia 4/36 (11.1%), peripheral neuropathy 2/36 (5.6%). Mild hypersensitivity to Rituximab was seen in 2/36 (5.6%) pts. Only 1 patient had cardiac toxicity in form of CHF. Our study showed response rates (94%) and toxicity profile similar to what has been reported in other studies with R-CHOP. The follow-up is too short to evaluate survival rates. Keywords: DLBCL, Rituximab, CHOP.