The present invention relates to a process for separating pyrite from sulfide ores and coal during flotation separation which comprises the depressing of pyrite with from about 0.05 to 0.75 kilograms per ton of concentrate solids using a pyrite depressant compounds selected from the group consisting of R1, R2, R3 N.sup.+ O.sub.2 H.sub.4 SR4X.sup.- (I) where R1, R2 and R3 are lower alkyls wherein the final sum of the carbon atoms is in a range of 3 to 6, R4 is selected from a group consisting of hydrogen (H) and amidine and X is chlorine, bromine or iodine, ##STR1## where Ro is a lower alkyl having carbon atoms in a range of 3 to 8 with 3 to 6 being preferred and a final pH in a range of 4 to 9 depending on the ore being processed, and therafter recovering the flotation concentrate thus obtained. As to group (I) compounds, 2-trimethylammonium-ethane isothiuronium dichloride (TMAE) as a pyrite depressant is surprisingly effective in pyrite removal being substantially independent of the pH values of the treated ore or coal, compatible with conventional collector reagents such as xanthates in the case of copper sulfide bearing ores as well as being substantially unobtrusive in not depressing other useful ore sulfides, including but limited to chalcopyrite, bornite chalcosite. Group (II) are more pH sensitive.