Enzyme activities of acid sphingomyelinase (ASM) were determined in various human cell-free body fluids, serum, cerebrospinal fluid, urine, salivary fluid, tear fluid, and synovial fluid, using assay buffers with or without Zn 2+-cation. Although ASM activity was not detected in the cerebrospinal fluid, the other fluids demonstrated significant enzyme activities of ASM. All ASMs detected in the fluids were stimulated by the addition of Zn 2+-cation, suggesting that those enzymes are secretory ASM derived from ASM gene. We suggest a possible enzymatic diagnosis of Niemann-Pick disease types A and B using those body fluids. Interestingly, salivary and tear fluids showed much higher activities of ASM than those of the other fluids. Because sphingolipids, especially sphingomyelin, are major constituents of a normal diet, especially, milk, eggs, and meat products, we suggest that ASM in the salivary gland may play an important role in the digestion of sphingomyelin in a normal diet.