According to personal experience, good clinical effects may be obtained by monocomponent insulin treatment, independently from strict immunological indications (i.e. high plasma-anti-insulin antibody titers). The present paper reports on a two daily injection treatment with monocomponent Semilente insulin (SeLe MC) in comparison with an earlier management with conventional retard insulins, in a group of 16 insulin dependent diabetics, selected among the most poorly controlled patients with unstable diabetes and/or high insulin requirement. In 6 subjects, after transfer to SeLe MC, it was observed a reduction in M bs, delta, and M delta indices of the glycemic regulation, indicating lower mean glycemic profiles with fewer irregularities. In 11 cases a marked improvement in the subjective symptomatology was noticed. Some minor hypoglycemic reactions induced to a reduction in the high insulin requirement in 8 cases. All but two patients had significant values of insulin IgG antibodies. The period of observation was too short to take in consideration an immunological modification, as an explanation of the present clinical results. However, these could be hypothetically referred to an amelioration in the releasing of endogenous insulin and/or in the hormone-receptor interaction as a consequence of treatment with monocomponent insulin preparations, in comparison to non purified conventional preparations. Treatment with SeLe MC seems to be suitable in particularly difficult control of the diabetes and in emergency situations.