Exposure to highly toxic chemicals may lead to acute life-threatening conditions that require early medical intervention. Correct interpretation of symptoms of intoxication is therefore highly important for decisions on triage, medical treatment and personal decontamination. Intoxication of organophosphorus compounds and opioids have shown similar symptoms while antidotes and the need for decontamination differs. Misinterpretation of symptoms may lead to increased risks for both patients and medical responders. In this report, the scientific understanding of symptom development after poisoning with highly toxic organophosphorus nerve agents and synthetic opioids of the fentanyl group has been compiled. Occurrence of symptoms described in scientific studies and reports from actual exposures were divided in three groups: 1. Unspecific symptoms 2. Shared symptoms for nerve agents and opioids 3. Nerve agent specific symptoms To enable operative use a practical guidance for differential diagnostics of the two groups of substances has been suggested. In addition to symptom interpretation, the potential of antidote treatment effects and laboratory diagnostics is included. Procedure for nerve agents 1. Symptom development including specific symptoms for nerve agents 2. Analysis of choline esterase activity in blood Procedure for opioids 1. Symptom development 2. Effect of antidote (naloxone) 3. Identification of compound metabolites