The hyperinsulinaemia and hypoglycaemia produced by malignant insulinomas pose a difficult therapeutic problem. The non-polar monoamine precursors 5-hydroxytryptophan, L-3,4dihydroxyphenylalanine and DL-tlireo-dihydroxyphenylserine are readily taken up by normal hamster pancreatic islets and are converted intracellularly to serotonin, dopamine and norepinephrine. These intracellular monoamines then inhibit glucose-stimulated insulin secretion. In the present study we have determined if the monoamine oxidase inhibitor pargyline, and monoamine precursors, could modify the severe hypoglycaemia of hamsters bearing a rapidly growing transplantable insulinoma. One hour after receiving the respective precursor there was an 11, 18, and 54-fold increase in the concentration of serotonin, dopamine or norepinephrine in the insulinomas. Twenty four hours after the administration of the respective precursors there were the following increases in plasma glucose in the respective groups: 5-hydroxytryptophan, 1.9 _+ 0.5 to 4.9 _+ 0.3 mmol/1 (mean _+ SEM); L-3,4-dihydroxyphenylalanine, 1.5 + 0.3 to 3.4 _+ 0.6 mmol/1; and DLthreo-dihydroxyphenylserine, 1.5 _+ 0.2 to 6.4 ___ 0.7 mmol/1. The change in plasma insulin concentration was statistically significant only in the group receiving DL-threo-dihydroxyphenylserine (229 + 59 to 81 _+ 42 mU/1). To determine if this therapeutic approach could modify the rapidly fatal outcome of the tumour-bearing hamsters, they received 0.154 mol/1 saline, DL-threo-dihydroxyphenylserine or pargyline plus DL-threo-dihydroxyphenylserine every two days. The survival of the groups (mean _+ SEM) was: saline 8.4 + 1.1 d; DL-threo-dihydroxyphenylserine 17.9 _+ 3.5 d; and pargyline plus DL-threo-dihydroxyphenylserine 24.4 _+ 5.5 d. The present study suggests that increasing the monoamine content of malignant insulinomas may favourably modify the course of these devastating tumours.