Screening of pooled urine samples was suggested during the Second World War as a method for reducing the cost of detecting syphilis in U.S. soldiers. Recently, pooling has been used in screening for human immunodeficiency virus (HIV) antibody to help curb the further spread of the virus. Pooling reduces the cost but also—and probably more importantly—offers a feasible way to lower the error rates associated with labeling samples when screening low-risk HIV populations. For example, given the limited precision of the presently available test kits, when the screened population has a prevalence of 4 per 1,000 (which is roughly the estimated U.S. prevalence), the probability that a sample labeled positive is antibody-free can be reduced from approximately 90% (if each sample is tested individually) to about 2%. Furthermore, screening pooled sera samples can also be used to reduce the probability that a sample labeled negative in fact has antibodies up to 40-fold in such a population—an important consideration when attempting to preserve the integrity of the blood supply. In this article we generalize some commonly used pooling procedures and introduce some new ones. We discuss and compare these procedures' relative merits and weaknesses under practical situations in the context of HIV screening. The proposed procedures can also be used and generalized to other medical and quality control applications.