This study compared the sensitivity of three methods: staphyloccocal clumping test, SCT (Sigma and Calbiochem-Behring, CBC, reagents); Thrombo-Wellcotest (TWT); and Dade fibrinogen degradation products detection set, to quantify fibrinogen/fibrin split products (FSP) in blood samples from 696 patients and 124 normal donors using fibrinogen as the reference value. The Dade method gave quantitative results closely approaching the stated amount of fibrinogen. The SCT using Sigma reagents gave higher "fibrinogen" values, while the CBC reagents gave markedly lower "fibrinogen" values. The TWT detected only 25% of the fibrinogen standard. Detection of FSP following plasmin digestion of fibrinogen varied considerably for each test. The TWT, insensitive to most of the native fibrinogen, detected most of the FSP following only 15 minutes of plasmin digestion. In contrast, both assays relying on the SCT were completely negative after 24 hours of plasmin digestion. All four methods yielded FSP titers of less than 10 micrograms/mL in 97 (78.2%) of 124 blood samples from normal donors. The SCT Sigma reagents consistently gave results of less than 10 micrograms/mL in all normal donors. No instance of an FSP value greater than 40 micrograms/mL was noted for the 124 normal donors. Of the 696 patient blood samples tested, the Dade assay gave the highest or equally highest (with respect to another FSP method) value in 604 (87%) cases; the Sigma SCT did so in 360 (52%); the TWT in 316 (45%); and the CBC assay in 184 (26%) cases. The Dade test classified the largest number of blood samples, 328 (47.1%), in the greater than 10 less than 40 micrograms/mL titer category; however, the proportion of cases (32.2%) in which this test yielded values greater than 40 micrograms/mL was about the same as those produced by the Sigma SCT (29.9%) and TWT products (25.8%). Thus, with the exception of the normal (less than 10 micrograms/mL) and the suspicious (10-40 micrograms/mL) range, all three methods (Dade, Sigma, and TWT) are comparable in their abilities to detect abnormal levels of FSP. In the normal range, the Dade method will yield results that are frequently in the suspicious range. The CBC was noticeably inferior in detecting both suspicious and frankly abnormal values of FSP. Eight patients with acute leukemia were monitored sequentially with FSP and fibrinopeptide A (FpA) assays during their first course of chemotherapy. In all instances, elevated FpA levels correlated with elevated FSP values, as determined by the Dade, Sigma, or TWT assays.