Cryptococcal antigen titers in 97 serum and 42 cerebrospinal fluid (CSF) specimens from 37 AIDS patients with culture-proven cryptococcal infection were determined with the Meridian kit (Meridian Diagnostics Inc., Cincinnati, Ohio) before and after treatment with pronase. The geometric mean titers before and after pronase treatment were 1:45 and 1:588 in serum and 1:97 and 1:79 in CSF, respectively. Only on serum (but not CSF) specimens after pronase treatment were (i) titers increased by 2 to 13 dilutions on 57% of the specimens, all of which had titers of less than or equal to 1:128 before pronase treatment, (ii) false-negative reactions on 27% of specimens before pronase treatment eliminated, all of which had titers from 1:4 to 1:4,096, (iii) prozone-like reactions (titer, less than or equal to 1:256) on 9% of the specimens before pronase treatment eliminated, and (iv) agglutination reactions on all specimens stronger and easier to interpret. Antifungal agents added to serum as well as freeze-thaw cycles did not change antigen titers in serum. After two separate tests, the same titers were obtained on 94% of 35 serum specimens that were treated with pronase and on 96% of 53 CSF specimens that were not treated with pronase. A total of 26 serum specimens and 28 CSF specimens from patients with no cryptococcal disease were negative before and after pronase treatment. The IBL kit (International Biological Labs Inc., Cranbury, N.J.) was compared with the Meridian kit on 41 serum specimens and 14 CSF specimens. Results from the two kits agreed on 54 and 68% of serum specimens and 86 and 93% of CSF specimens before and after pronase treatment, respectively. The IBL kit generally produced higher titers on specimens in disagreement and produced no prozone-like reactions. Routine pronase treatment of serum is recommended with the Meridian kit in order to eliminate false-negative and unclear agglutination reactions by producing a consistent interpretation of agglutination reactions. CSF specimens do not require pronase treatment. Titer results produced by the kits from the two different manufacturers varied considerably: the kits should not be used interchangeably for determining antigen titers in serum specimens.