Background:Selective in-vivo anti-fungal action of potassium iodide (KI) is an enigma, but circumstantial evidences strongly indicate some immune mechanism.Aim:Study was to demonstrate in-vitro immune-modulating role of KI.Materials and Methods:In identical test conditions keeping appropriate control, different immunological tests were performed with and without 0.1% effective concentration of KI. i) Sera from Coombs positive mothers were treated with O, Rh-positive erythrocyte suspensions along with Coombs’ sera (CS)/Bovine albumin (BA)/KI. ii) Amboceptor and complement (C) mixtures were titrated for hemolysis with or without KI. iii) Suspension of Salmonella Typhi with positive sera from enteric cases and C + KI was incubated at 37°C for 30 minutes, then sub-cultured on MacConkey Agar. iv) Positive serum from chronic muco-cutaneous candidiasis patient was treated with suspension of candida isolate and C + KI at 37°C for 30 minutes then sub-cultured to note variations in colony counts. The data was analyzed by Fishers exact test using Graphpad Prism 5 version 5.00 (California USA)Results:i) KI like BA or CS showed hemagglutination. ii) C-mediated hemolysis was inhibited in presence of KI. iii) C-mediated lysis of S. typhi was partially enhanced by KI showing reduced number of colonies; iv) while lysis of candida was reduced.Conclusions:KI increases avidity of some immune reactions including C-mediated cell lysis. An increase or decrease of cell-lysis resulted by KI probably mediates by altered access of C-binding receptors. Thus, hypothetically, a non-protective Splendore Hoeppli-like deposit around fungus may turn into protective immune mechanism by influence of KI.