The identity and genetic origins of the nonspecific orthophosphate monoesterases with an acid pH optimum--the acid phosphatases--are now becoming clear. They form a family of genetically distinct isoenzymes, many of which show significant posttranslational modification. Four true isoenzymes exist. The erythrocytic and lysosomal forms show widespread distribution and are expressed in most cells; in contrast, the prostatic and macrophagic forms have a more limited expression. The erythrocytic and macrophagic forms are distinguished from the others in resisting inhibition by dextrorotatory tartrate. The prostatic form has long been used as a marker for prostatic cancer and the macrophagic forms have been linked with miscellaneous disorders, notably increased osteolysis, Gaucher's disease of spleen, and hairy cell leukemia, whereas the normal levels of intravesical lysosomal acid phosphatase in I cell disease pointed the way toward the mechanisms underlying its intracellular processing.