After quantitating immunoglobulins G, A, and M and complement C3c and C4 in serum by using a laser nephelometer coupled with a data processor, I compared these results with values obtained by an early-readout radial immunodiffusion method. Day-to-day precision was better for nephelometry than for radial immunodiffusion for all proteins analyzed. The average coefficient of variation was 6.0% for nephelometry and 9.9% for radial immunodiffusion. Comparison of these methods gave ranked correlation coefficients of 0.945, 0.981, 0.932, 0.803, and 0.792 for IgG, IgA, IgM, C3c, and C4, respectively. Nephelometry gave significantly higher values than radial immunodiffusion for IgG, IgA, IgM, and C3c, and significantly lower values for C4 (p less than 0.001). Part of this bias was found to be due to the equation programmed in the data processor for calculating the standard curves. Within 95% limits, nephelometry gave higher normal ranges than radial immunodiffusion for IgG, IgA, and IgM. Other possible factors that can produce this bias are discussed.