In the process of a scientific experiment a workflow is executed multiple times using various values of the parameters of activities. For real-world workflows that may contain hundreds of activities, each having several parameters, it is practically not feasible to conduct a parameter sensitivity study by simply following a ”brute-force approach” (that is experimental evaluation of all possible cases). We believe that a heuristic-guided approach enables to find a near-optimal solution using a reasonable amount of resources without the need for the evaluation of all possibilities. In this paper we present a novel methodology for determination of parameter significance of scientific workflows that is based on Ant Colony Optimization (ACO). We refer to our methodology, which is a customization of ACO for Parameter Significance determination, as ACO4PS. We use ACO4PS to identify (1) which parameter strongly affects the overall result of the workflow and (2) for which combination of parameter values we obtain the expected result. ACO4PS generates a list of all workflow parameters sorted by significance as well as is capable of generating a subset of significant parameters. We empirically evaluate our methodology using a real-world scientific workflow that deals with the Non-Invasive Glucose Measurement.