Two-dimensional (2-D) gel analysis was used to examine differences in the levels of 19 plasma proteins: before and after an acute inflammatory reaction (parenteral typhoid vaccination) in normal subjects, between rheumatoid arthritis (RA) patients and normals and in RA patients treated with tenidap (120 mg) and piroxicam (20 mg). Typhoid vaccination increased levels of SAA, haptoglobin alpha(1), haptoglobin alpha(2), haptoglobin beta and alpha(1)-anti-chymotrypsin but decreased transthyretin and apolipoprotein E. In RA patients, serum amyloid A (SAA), haptoglobin alpha(2), haptoglobin beta, alpha(1)-antichymotrypsin and C3 proactivator levels were elevated while apolipoprotein A-I, apolipoprotein A-IV, transthyretin, Gc-globulin, alpha(2)-HS glycoprotein, alpha(2)-macroglobulin and alpha(1)-B glycoprotein levels were decreased, compared to normals. Compared to piroxicam, tenidap lowered levels of alpha(1)-antiprotease and SAA but raised the levels of transthyretin, Gc-globulin, alpha(2)-HS-glycoprotein and alpha(2)-macroglobulin in RA. patients. C-reactive protein (CRP) could not be quantified on 2-D gels but, when measured by rate nephelometry, levels were reduced after treatment with tenidap compared to piroxicam. The general pattern of the acute phase protein response to an acute inflammatory response to typhoid vaccination is similar to that in the chronic inflammatory condition, RA. The impact of tenidap on both positive and negative acute-phase proteins in RA patients could clearly be distinguished from that of piroxicam.