Proinflammatory cytokine responses might occur in elderly individuals with cardiovascular (CV) disease, cerebro-vascular (CVA) disease, and/or pulmonary disease (PD). Spiritual activation is an important coping mechanism, since psychiatric depression is an important risk factor for these individuals. Thirty-three very elderly individuals (87 ± 8 years) with previous CVD, CVA and/or PD participated in weekly 30 minute sermons by chaplains for over 20 months of chaplain liturgy (CL group). All underwent Holter ECG during the procedures and cardiac autonomic activities were assessed by maximum entropy analysis. Plasma IL-10 and IL-6 levels were compared with 26 age-matched (85 ± 10 years) individuals who did not participate in these activities (non-CL group). Both high frequency (HF) and pNN50 of heart rate variability (HRV) were higher in the CL group than in the non-CL group (HF, 190 ± 55 versus 92 ± 43 nu, P < 0.05; pNN50, 10.5 ± 16% versus 3.6 ± 3.8%, P < 0.05), whereas LF/HF was lower (1.4 ± 1.5 versus 2.2 ± 2.8, P < 0.05). Levels of IL-10/IL-6 were higher in the CL group (3.96 ± 5.0 versus 1.79 ± 1.6, P < 0.05). Hospitalization rates due to CVD and/or PD were lower in the CL group than in the non-CL group (4/33 versus 11/26, P < 0.05). We conclude that spiritual activation can modify proinflammatory cytokines and suppress CVD, CVA and/or PD via vagal modifications. Spiritual activation might be helpful for health in these very elderly individuals.