Finger puncture sampling was used to obtain 100 μl of plasma from young children. Both salicylic acid (SA) and acetaminophen (APAP) were measured concomitantly by a high pressure liquid chromatography technique which used an absorbance detector (λ = 254 nm) in series with a fluorescence monitor (excitation, 305 nm; emission, 320 nm). The lower limit of detection for APAP and SA was 0.3 μg/ml plasma. All samples were eluted within 9 min by using a McOH:H2O:PIC A (tetrabutylammonium phosphate) solvent mixture. Acetylsalicylic acid could also be measured. Pretreatment blood samples from febrile children showed that about 50% had previously received either aspirin or APAP. Historical information was not a reliable index of prior antipyretic therapy. The method was thus applicable for screening of apparently naive subjects. The concomitant disposition characteristics of both drugs are shown for two children. An average APAP plasma half-life of 1.9 hr was found for 19 febrile children between the ages 2 and 7 years. Pharmacokinetic and pharmacodynamic data can now be collected in febrile children as a basis for therapeutic monitoring of these two widely used drugs.