The objective of the study was to test L-methioinine as a possible immune supportive supplement in HIV infected patients by means of a clinical study. A double-blind, placebo-controlled study was designed. The patients (n = 253) from four different trial centres were randomly divided into two groups, active and placebo, and regularly assessed by clinical and safety parameters. After six months from commencement, clinically and statistically significant differences were observed. The females of the active treatment group presented with a decreased level of decline in their CD4 counts (p = 0.0027), so also the patients of Centre 1 (p = 0.0377). All patients were placed onto active treatment after 12 months and were followed up for 48 months after the trial started. The same tendencies could be observed in the group as a whole, with no serious side effects directly associated to treatment. The study confirmed the supportive role of L-methionine in immune-compromised or deficient patients.