We studied three methods (rate nephelometry, radial immunodiffusion, and trypsin-inhibitory capacity) for their ability to detect those individuals with a deficiency of alpha1-antitrypsin. The phenotype represented in 170 serum samples was determined by isoelectric focusing as the reference method. All three methods correctly identified Pi Z, Pi S, and Pi SZ phenotypes but varied in their ability to detect Pi MZ and Pi MS phenotypes. The rate-nephelometric method was the least sensitive in detecting Pi MZ and Pi MS variants because of the inappropriately low reference interval suggested by the manufacturer. We found that the three screening methods are comparable when the limiting values are properly selected. We suggest that the reference value for the rate-nephelometric method be increased from 0.85 g/L to 1.40 g/L to improve the sensitivity of the test.