During the period 1/1990-9/1995 a total of 311 RA patients were challenged 458 times with 52 different COMBOs. As the first COMBO methotrexate (MTX), sulphasalazine (SSZ), im gold (GOLD), and hydroxychoroquine (HCQ) were combined with each other in 272/311 cases. The respective six and 12 months survivals of these COMBOs were 68.6% (95% CI 63.0% to 74.3%) and 53.6% (95% CI 47.4% to 59.9%). Inefficacy (27.9%), rather than adverse events (23.5%) or other causes (16.9%) was the leading reason for the discontinuations. Only in five cases (1.8%) these COMBOs were discontinued due to a remission. Not a single adverse event related to a COMBO treatment was judged as serious. The mean survival time for COMBOs including MTX (24.0 months; 95% CI 20.6 to 27.4) was statistically significantly longer than the respective time for COMBOs without MTX (14.5 months; 95% CI 11.2 to 17.7). We conclude that, when meticulously monitored, the treatment with COMBOs is safe. However, their efficacy on patients with advanced RA is modest. The survival time for COMBOs including MTX is longer than COMBOs without MTX.