The effect of insulin treatment with 2 different insulin regimens on the plasma concentrations of lipoproteins and apolipoproteins A1 and B was studied in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycaemic agents. The investigation was performed as a randomized crossover study with treatment periods of 8 weeks. Insulin was given either as mainly intermediate acting insulin before breakfast and dinner (2-dose insulin) or as regular insulin preprandially with intermediate acting insulin at bedtime (4-dose insulin). A similar improvement in glycaemic control was obtained with both insulin regimens. On treatment with oral agents the patients were found to have higher total plasma triglycerides and lower plasma high density lipoprotein (HDL) cholesterol than a matched non-diabetic control group. Insulin treatment almost completely normalized these lipid disturbances by reducing mean total plasma triglycerides with 36% and increasing plasma HDL cholesterol with 20% on 2-dose and 17% on 4-dose. The triglyceride concentration in the very low density lipoprotein (VLDL) fraction was reduced. Mean plasma low density lipoprotein (LDL)-cholesterol was not affected by any treatment. There was an increase of similar magnitude in both HDL2 and HDL3 concentrations but only the change in the HDL3 subfraction was statistically significant. Mean plasma apolipoprotein A1 concentration increased with 9% (P less than 0.05) while there was no significant change in the plasma apolipoprotein B concentration. The changes in the plasma concentrations of lipoproteins and apolipoproteins A1 and B were almost identical on 2- and 4-dose insulin.(ABSTRACT TRUNCATED AT 250 WORDS)