Four immunochemical methods for measuring C-reactive protein (CRP) in plasma were compared: radial immunodiffusion (RID), electroimmunoassay (EIA), immunoturbidimetry (IT), and laser nephelometry (LN). Close agreement was found between RID and EIA (EIA = 0.96 RID + 7.7 mg/L, r = 0.977, n = 100), IT and EIA (EIA = 1.11 IT - 15.8 mg/L, r = 0.951, n = 100), IT and RID (RID = 1.10 IT - 11.5 mg/L r = 0.959, n = 94). In initial studies in 1983, LN showed good agreement with RID (LN = 0.98 RID + 11.9 mg/L, r = 0.973, n = 60). Since then, normal CRP values measured by LN have tended to increase and, at the time of the present study (1986), LN agreed poorly with other methods. The reason for this change is obscure. Having excluded the possibility of enzymatic degradation of CRP, we conclude that instrumentation problems are involved, and therefore we no longer use this method.