5‐Hydroxytryptamine and a number of (+)‐lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5‐hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10−16 m lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one‐half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5‐hydroxytryptamine blocking action. This group consisted of 1‐methyl‐, 1‐acetyl‐, and 2‐bromo‐lysergic acid diethylamide and 1‐methyl‐lysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10−4 m, and it blocked 5‐hydroxytryptamine in a molar ratio of about one to one.